Mal-PEG8-acid is a PEG linker containing a maleimide group with a terminal carboxylic acid. The hydrophilic PEG spacer increases solubility in aqueous media. The maleimide group will react with a thiol group to form a covalent bond, enabling the connection of biomolecule with a thiol. The terminal carboxylic acid can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable amide bond.
Mal-PEG8-acid is a PEG-based PROTAC linker can be used in the synthesis of PROTACs.
Mal-PEG8-acid is a key building block in the synthesis of antibody-drug conjugates for the treatment of cancer. The target molecule 7 is obtained in a single step by coupling the amino group of intermediate 40 to Mal-PEG8-acid following its in situ activation (with EDC·HCl) in solution. The PEG8 moiety in the structure provides the entire drug-linker with the necessary hydrophilicity and flexibility to improve solubility and pharmacokinetic properties. The terminal maleimide (mal) group is used for subsequent site-specific coupling with the thiol groups on the antibody, thereby forming the complete antibody-drug conjugate[1].
[1] William R. F. Goundry*, & Bertrand Cottineau, (2024). Route Design and Scale-Up of a Topoisomerase I Inhibitor Antibody–Drug Conjugate Payload. Organic Process Research & Development, 28 6, 2355–2366.
https://doi.org/10.1021/acs.oprd.4c00175
